The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.
The aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD.
Eight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4-5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5mM, n?6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed.
Indole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motifreduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier.Redβ is a single strand annealing protein from bacteriophage λ that binds loosely to ssDNA, not at all to pre-formed dsDNA, but tightly to a duplex intermediate of annealing. As viewed by electron microscopy, Redβ forms oligomeric rings on ssDNA substrate, and helical filaments on the annealed duplex intermediate. However, it is not clear if these are the functional forms of the protein in vivo. We have used size-exclusion chromatography coupled with multi-angle light scattering, analytical ultracentrifugation and native mass spectrometry (nMS) to characterize the size of the oligomers formed by Redβ in its different DNA-bound states. The nMS data, which resolve species with the highest resolution, reveal that Redβ forms an oligomer of 12 subunits in the absence of DNA, complexes ranging from 4 to 14 subunits on 38-mer ssDNA, and a much more distinct and stable complex of 11 subunits on 38-mer annealed duplex. We also measure the concentration of Redβ in cells active for recombination and find it to range from 7 to 27 μM. Collectively, these data provide new insights into the dynamic nature of the complex on ssDNA, and the more stable and defined complex on annealed duplex.Exposure to a maternal high-fat diet (HFD) predisposes offspring to nonalcoholic fatty liver disease.
The aim of this study was to explore whether milk fat globule membrane (MFGM) supplementation during suckling exerts a long-term protective effect on hepatic lipid metabolism in adult offspring exposed to maternal HFD.
We fed 5-week-old female C57BL/6Jmice either a HFD (60%kcal fat) or control diet (CD; 16.7%kcal fat) for 3 weeks before mating, as well as throughout gestation and lactation. After delivery, male offspring from HFD dams were supplemented with 1g/(kg body weight?day) MFGM (HFD+MFGM group) or the same volume of vehicle (HFD group) during suckling. Male offspring from CD dams were also supplemented with vehicle during suckling (CD group). All offspring were weaned onto CD for 8 weeks. Histopathology, metabolic parameters, lipogenic level, oxidative stress, and mitochondria function in the liver were analyzed. A 1-way ANOVA and a Kruskal-Wallis test were used for multi-group comparisons.
Asfenses and improving mitochondrial function.
MFGM supplementation during suckling ameliorates maternal HFD-induced hepatic steatosis in mice via suppressing de novo lipogenesis, reinforcing antioxidant defenses and improving mitochondrial function.We examined the efficacy and tolerability of calcitonin gene-related peptide targeted monoclonal antibodies (CGRP-targeted mAbs) as add-on therapy for patients with chronic migraine (CM) undergoing treatment with onabotulinumtoxinA(onabot) who require additional preventive therapy.
We reviewed medical records of patients with CM receiving treatment with onabot who were subsequently prescribed a CGRP-targeted mAb medication. The primary outcome was the change in number of monthly headache days (MHDs) reported. Secondary outcomes were change in headache pain severity, discontinuation due to lack of tolerability, and severe adverse events.
Of 153 patients, 111 (72.5%) reported a decrease in either MHDs or headache pain severity, with documentation of MHDs in 66 patients. Of these 66 patients, average MHDs prior to initiating onabot treatment was 25.7. After onabot treatment, an average decrease of 10.9 MHDs was reported (p?&lt;?0.001). After the addition of a CGRP-targeted mAb medication, patients experienced a further decrease of 5.7 MHDs (p?&lt;?0.001). With combined therapy, patients reported a total decrease of 16.6 MHDs (p?&lt;?0.001). Adverse effects occurred in 13 patients (8.5%) after addition of the CGRP-targeted mAb and included constipation, injection site reaction, and/or fatigue. No serious adverse events were reported.
Adding a CGRP-targeted mAb to onabot in patients with CM was associated with further reductions in MHDs without major tolerability issues across a range of mAbs. This retrospective review supports the conduct of a well-designed double-blind study adding a CGRP-targeted mAb or placebo to onabot.
Adding a CGRP-targeted mAb to onabot in patients with CM was associated with further reductions in MHDs without major tolerability issues across a range of mAbs. This retrospective review supports the conduct of a well-designed double-blind study adding a CGRP-targeted mAb or placebo to onabot.Handgrip strength (HGS) is used to assess muscle strength, which is an important indicator of health status in older adults.
We evaluated associations of demographic, anthropometric, clinical, and nutritional factors with muscle strength in community-dwelling elderly adults.
This population-based cross-sectional study employed the 2014-2015 Israeli Health and Nutrition Survey in the Elderly (n=1039, age?65 y, 46.7% males, 9.9% Arabs). Trained personnel performed face-to-face interviews that focused on health and nutrition status, as well as anthropometric measurements and examinations. HGS was measured in the dominant hand 3 times using a digital grip strength dynamometer; the highest result was reported. Dietary intake data were collected using single-day 24-h recall. Multivariable logistic regressions were used to explore factors associated with low HGS (&lt;27kg for men and&lt;16kgfor women).
HGS measurements were completed by 704 participants. https://www.selleckchem.com/products/adenosine-5-diphosphate-sodium-salt.html Following adjustment for several factors, higher prevalence of low HGS was significantly associated with age (OR 1.